Combinatorial chemistry Reaction optimization

Medicinal chemistry makes use of solid phase combinatorial chemistry as a (rapidly maturing) tool for lead discovery and optimization. Metathesis reactions are obviously useful in this context [45] as they can be used ... 

Q. Liu, L. A Comparison of Various FTIR and FT Raman Methods Applications in the Reaction Optimization Stage of Combinatorial Chemistry, J. Comb. Chem. 1999, 7, 46. 

What do we mean by a modeling infrastructure Given the situation in which some high-level chemistry is hypothesized, too much data exist for one scientist to analyze. For example, the 820 reactions of the rubber components formulation involve over 100 chemical species. It is impossible for one person to write and solve over 100 coupled differential equations without making mistakes. It would take nearly 3 months to explore one scenario. So we have built an environment where the scenario is specified and the information is automatically translated into equations, the parameters are optimized, and the modeled results are compared with data. This way a scenario can be analyzed in a few hours instead of 3 months. This is the type of modeling highway that can get the most out of combinatorial chemistry situations. 

The preparation of peptides and nucleotides involves the iterative repetition of three simple steps monomer activation, coupling to the growing chain, and deprotection to unmask a new reactive terminus. The arithmetical demon of linear syntheses, whereby the overall yield decreases exponentially with any loss in yield for each cycle, had forced chemists to perfect these reactions to the point of being practically quantitative. The availability of such robust protocols was a necessary prerequisite for combinatorial chemistry. Outside the peptide and nucleotide areas, synthesis of a library is often far less time consuming than the development of optimized reaction conditions. 

The realm of combinatorial chemistry is covered by a wide umbrella of techniques that include both solution phase and solid phase synthesis. The revival of solid phase synthesis has led to great interest in the development of analytical methods to monitor the reaction directly on the polymer support during the course of combinatorial syntheses. These techniques have a significant advantage compared to cleave-and-analyze characterization, particularly for optimizing reaction conditions. 

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